This invention relates to the rapid analysis of complex spectra produced by mixtures that contain multiple components that produce overlapping signal information.
The field of analytical chemistry involves the processes of sample collection, sample preparation, sample/constituent detection, data reduction, and statistics. For years method and instrument developers have made tradeoffs among the principal components that drive the analytical process, namely, the sample analysis rate, measurement sensitivity, and measurement precision and accuracy. To improve the overall sample analysis rates, much effort has been directed toward automation of the overall analytical process in an attempt to reduce the time of analysis and cost. Although automation has led to some improvements in precision and reductions in personnel costs, other attributes of the analytical process are much less affected, for example measurement sensitivity and accuracy.
Over the years, the term spectroscopy has come to mean the study (i.e., the identification, quantification, and theory) of electromagnetic radiation (including .gamma.-ray, x-ray, ultraviolet/visible (UV/VIS), infrared (IR), microwave, electron spin, and nuclear magnetic resonance) as well as acoustic waves, electrons, and mass. In each of these spectroscopies, a source is used to probe specific regions within molecules or atoms.
For example, in atomic spectroscopy, flames, lasers, or plasmas, as well as other types of sources, are used to excite atom(s) that then absorb, emit, or fluoresce energy at characteristic wavelengths. This type of spectroscopy produces atomic species that produce narrow band peaks (called "lines") as opposed to molecular spectroscopy, e.g., UV/VIS or IR, which produces broad peaks ("bands") from molecules that have absorbed energy between 10 nm and 100 .mu.m.
Mass spectrometry (MS) also employs a source to ionize molecules or atoms. Such sources include electron impact filaments, chemical ionization, or lasers, as well as other known sources. The gaseous ions are then separated by their mass-to-charge ratio (m/z) and detected as narrow band peaks. The output from a mass spectrometer is typically displayed as line signals.
In spectrometry, compounds or atoms are identified by their characteristic spectral peaks and their concentrations are determined from the corresponding peak intensities. For example, in mass spectrometry, an organic compound is ionized with the resulting gaseous fragment ions separated according to their differing masses and charges to form a characteristic "fingerprint." This fingerprint is compared to a set of patterns in a library and is identified on a best-fit probabilistic matched set basis, with a corresponding major ion current used to determine compound or atom concentration.
Mass spectrometry currently requires a separation step prior to analysis since simultaneous multiple compound detection results in many more fragment ions being produced than the probabilistic statistics can conventionally handle. Both gas and liquid chromatographies, as well as capillary electrophoresis separation, traditionally have been used prior to MS analysis for biological, chemical, environmental, petroleum, forensic, and many other types of analyses.
For example, thermal desorption gas chromatography/mass spectrometry (TDGC/MS) methods have recently been used to analyze nearly all U.S. Environmental Protection Agency (EPA) listed pollutant organics. The data from these methods have been accepted by both state and federal regulators and have supported numerous hazardous waste site investigations and cleanups. TDGC/MS methods can reduce the time of analysis (Robbat, Jr. et al., Analytical Chemistry, 64, 358-362, 1992; Robbat, Jr. et al., Analytical Chemistry, 64, 1477-1483, 1992; and Robbat et al., Hazardous Waste and Hazardous Materials, 10:461-473, 1993), but are limited in that they require a sample preparation step followed by gas chromatography separation of the individual constituents within the sample, and are restricted in the number of compounds they can analyze at one time.
Although standard laboratory instruments and methods provide good data quality, they do not meet the required sample throughput rates and trade measurement sensitivity for measurement precision and accuracy. To be cost-effective, current technologies do not provide compound-specification in "real" or "near real-time."
Various methods have been developed to improve and expedite the interpretation of mass spectra. For example, Gray et al., U.S. Pat. No. 5,453,613, describes a method of re-sorting mass spectra data files from chronological order to first ion-mass order and then to chronological order within separate ion-mass groupings. Local maxima are identified and then sorted and partitioned to obtain a set of deconvoluted spectra in which each element in the set is an identifiable compound. Compounds are then matched to reference spectra by conventional probabilistic matching routines.
Enke et al., U.S. Pat. No. 5,175,430, describes a time/separation spectral array detection system in conjunction with mass spectrometry to improve compound identification and decrease analysis time. Enke calls this time-compressed gas chromatography/mass spectrometry. Enke et al. note that the software approach of deconvolution has "not been significantly employed," because of the "insufficient quality and density in the data available." Enke et al. solve this problem with a new apparatus (i.e., a hardware approach) that allows time-separation spectral detection to provide spectral data of high quality and density.